The presentation speech was delivered by Peter Reichard of the Karolinska Medico-Chirurgical Institute. Note the opening line that refers to Monod's famous quote"What is true of E. coli is also true of the elephant." It was 1971 and Chance and Necessity had just come out. For years scientists had thought that the action of hormones demonstrated that so-called "higher" organisms used higher-level processes to regulate metabolism. Hormones needed whole tissues and organs to show an effect. What Sutherland proved was that hormones work at the cellular and molecular level just like the molecules that regulated activity in bacteria.

Your Majesty, Your Royal Highnesses, Ladies and Gentlemen,

What applies to bacteria also applies to elephants. This free quotation after the French Nobel prize winner, Jacques Monod, illustrates with some exaggeration one important principle of biology: that of the identity of the fundamental life processes.

Yet one need not be a Nobel prize winner to know the difference between bacteria and an elephant. The latter is not only much larger. The decisive difference lies in the fact that bacteria are unicellular organisms and that all the functions of life are contained in a single cell. In higher organisms on the other hand, there occurs a division of labor between different types of highly specialized cells. Nevertheless, the elephant must function as an integrated unity. The cells in the different organs must be coordinated in such a way that they rapidly adapt to the changing requirements of the environment.

The hormones form part of such a coordinating system. Among other things, the difference between a bacterium and an elephant lies in the fact that the latter - as well as all of us here - for the sustainment of his life is completely dependent of the proper function of hormones, while bacteria can do without them.

What then is the function of hormones? Ever since the first hormone was discovered about 70 years ago this has been a central theme of research for many scientists. This question is also of considerable medical importance. Many diseases are hormone diseases, amongst them diabetes. In spite of this the mechanism of hormone action remained a complete mystery until recently. The answer did not come until Earl Sutherland started his investigations on the function of the hormone epinephrine.

This hormone is produced in the adrenal glands and is transported to different organs of the body by the blood. It is formed in increased amounts during stress and adapts the individual to new situations. One of its important functions lies in the liberation of glucose inside the cells for the production of energy. Epinephrine serves as a chemical signal, as a messenger, which is sent out from the adrenals to activate different organs essential for the defense of the individual.

Sutherland investigated the effect of epinephrine on the formation of glucose in liver and muscle cells. He discovered a new chemical substance which serves as an intermediate during the function of the hormone. This substance is called cyclic AMP. It transmits the signal from epinephrine to the machinery of the cell, and Sutherland therefore called it a "second messenger". Furthermore, Sutherland made the important discovery that cyclic AMP is formed in the cell membrane. This means that epinephrine never enters the cell. We may visualize the hormone as a messenger which arrives at the door of the house and there rings the bell. The messenger is not allowed to enter the house. Instead the message is given to a servant, cyclic AMP, which then carries it to the interior of the house.

Sutherland suggested already around 1960 that cyclic AMP participates as a second messenger in many hormone mediated reactions, and that its effect thus is not limited to the action of epinephrine. First this generalization was not willingly accepted by the scientific community, since it was difficult to visualize how a single chemical substance could give rise to all the diverse effects mediated by various hormones. By now Sutherland and many other scientists have provided convincing evidence, however, that many hormones exert their effects by giving rise to the formation of cyclic AMP in the cell membrane. Sutherland had discovered a new biological principle, a general mechanism for the action of many hormones.

How can one then explain the specificity of different hormones? A good part of the explanation lies in the fact that different cells in their membranes possess specific receptors for various hormones. The different messengers thus must find their way to the right door in order to deliver their messages.

Cyclic AMP was discovered in connection with investigations concerning the function of hormones. It came therefore as a big surprise when Sutherland in 1965 reported that cyclic AMP also occurred in bacteria which apparently had no use for hormones. It was soon found that cyclic AMP was produced by other unicellular organisms, too. In all these cases cyclic AMP was shown to have important regulatory functions which aid the cells in their adaptation to the environment. Maybe we can look upon cyclic AMP as the first primitive hormone, regulating the behaviour of unicellular organisms. We then may look upon the true hormones of higher organisms as components of an overriding principle which was added during the course of evolution. Thus the difference between uni- and multicellular organisms does not, after all, appear to be so great, and with respect to cyclic AMP we can turn around Monod's dictum and say that what applies to elephants also applies to bacteria.

Dr. Sutherland,

Hormones were known in biology and medicine for a long time. The mechanism for hormone action remained a mystery, however, until you discovered cyclic AMP and its function as a second messenger. In recent years it has become apparent that cyclic AMP also serves as an important regulatory signal in microorganisms, and that its action thus is not limited to the function of hormones. When you discovered cyclic AMP you discovered one of the fundamental principles involved in the regulation of essentially all life processes. For this you have been awarded this year's Nobel prize in physiology or medicine. On behalf of the Karolinska Institute I wish to convey to you our warmest congratulations, and I now ask you to receive the prize from the hands of his Majesty the King.

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Principles of Biochemistry 5th edition

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Some readers of this blog may be under the impression that my personal opinions represent the official position of Canada, the Province of Ontario, the City of Toronto, the University of Toronto, the Faculty of Medicine, or the Department of Biochemistry. All of these institutions, plus every single one of my colleagues, students, friends, and relatives, want you to know that I do not speak for them. You should also know that they don't speak for me.

Superstition

Quotations

The old argument of design in nature, as given by Paley, which formerlyseemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.

Charles Darwin (c1880)Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.

Charles Darwin (1859)Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...

Quotations

I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory.

The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change.

Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance.

The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat.

Quotations

My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.

Jerry Coyne
Why Evolution Is TrueI once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.

Sydney Brenner
TIBS Dec. 2000
It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations

Douglas Futuyma
One of the most frightening things in the Western world, and in this country in particular, is the number of people who believe in things that are scientifically false. If someone tells me that the earth is less than 10,000 years old, in my opinion he should see a psychiatrist.

Francis Crick
There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.

Sydney Brenner
An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist

Richard Dawkins
Another curious aspect of the theory of evolution is that everybody thinks he understand it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.

Jacques Monod
The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.